Processes, systems, and apparatus for cyclotron production of technetium-99m

ABSTRACT

A system for producing technetium-99m from molybdate-100. The system comprises: a target capsule apparatus for housing a Mo-100-coated target plate; a target capsule pickup apparatus for engaging and delivering the target cell apparatus into a target station apparatus; a target station apparatus for receiving and mounting therein the target capsule apparatus. The target station apparatus is engaged with a cyclotron for irradiating the Mo-100-coated target plate with protons. The irradiated target capsule apparatus is transferred to a receiving cell apparatus comprising a dissolution/purification module for receiving therein a proton-irradiated Mo-100-coated target plate. A conveyance conduit infrastructure interconnects: (i) the target capsule pickup apparatus with the target station apparatus, (ii) the target station apparatus and the receiving cell apparatus; and (iii) the receiving cell apparatus and the dissolution/purification module.

TECHNICAL FIELD

The present disclosure pertains to processes, systems, and apparatus,for production of technetium-99m. More particularly, the presentpertains to production of technetium-99m from molybdenum-100 usingaccelerators such as cyclotrons.

BACKGROUND

Technetium-99m, referred to hereinafter as Tc-99m, is one of the mostwidely used radioactive tracers in nuclear medicine diagnosticprocedures. Tc-99m emits readily detectable 140 keV gamma rays and has ahalf-life of only about six hours, thereby limiting patients' exposureto radioactivity. Depending on the type of nuclear medicine procedure,Tc-99m is bound to a selected pharmaceutical that transports the Tc-99mto its required location which is then imaged by radiology equipment.Common nuclear medical diagnostic procedures include tagging Tc-99m tosulfur colloids for imaging the liver, the spleen, and bone marrow, tomacroaggregated albumin for lung scanning, to phosphonates for bonescanning, to iminodiacetic acids for imaging the hepatobiliary system,to glucoheptonates for renal scanning and brain scanning, todiethylenetriaminepentaacetic acid (DPTA) for brain scanning and kidneyscanning, to dimercaptosuccinic acid (DMSA) for scanning the renalcortex, to red blood cells for blood pool scanning of the heart, tomethoxy isoburyl isonitrile (MIBI) for imaging myocardial perfusion, forcardiac ventriculography, and to pyrophosphate for imaging calciumdeposits in damaged hearts. Tc-99m is also very useful for detection ofvarious forms of cancer for example, by identification of sentinalnodes, i.e., lymph nodes draining cancerous sites such as breast canceror malignant melanomas by first injecting a Tc-99m-labeled sulfurcolloid followed by injection of a Tc-99m-labeled isosulfan blue dye.Immunoscintigraphy methods are particularly useful for detectingdifficult-to-find cancers, and are based on tagging of Tc-99m tomonoclonal antibodies specific to selected cancer cells, injecting thetagged monoclonal antibodies and then scanning the subject's body withradiology equipment.

The world's supply of Tc-99m for nuclear medicine is currently producedin nuclear reactors. First, the parent nuclide of Tc-99m, molybdenum-99(referred to hereinafter as Mo-99) is produced by the fission ofenriched uranium in several nuclear reactors around the world. Mo-99 hasa relatively long half life of 66 hours which enables its world-widetransport to medical centers. Mo-99 is distributed in the form ofMo-99/Tc-99m generator devices using column chromatography to extractand recover Tc-99m from the decaying Mo-99. The chromatography columnsare loaded with acidic alumina (Al₂O₃) into which is added Mo-99 in theform of molybdate, MoO₄ ²⁻. As the Mo-99 decays, it forms pertechnetateTcO₄ ⁻, which because of its single charge is less tightly bound to thealumina column inside of the generator devices. Pulling normal salinesolution through the column of immobilized Mo-99 elutes the solubleTc-99m, resulting in a saline solution containing the Tc-99m as thepertechnetate, with sodium as the counterbalancing cation. The solutionof sodium pertechnetate may then be added in an appropriateconcentration to the organ-specific pharmaceutical “kit” to be used, orsodium pertechnetate can be used directly without pharmaceutical taggingfor specific procedures requiring only the [Tc-99m]O₄ ⁻ as the primaryradiopharmaceutical.

The problem with fission-based production of Tc-99m is that the severalnuclear reactors producing the world-wide supply of Mo-99 are close tothe end of their lifetimes. Almost two-thirds of the world's supply ofMo-99 currently comes from two reactors: (i) the National ResearchUniversal Reactor at the Chalk River Laboratories in Ontario, Canada,and (ii) the Petten nuclear reactor in the Netherlands. Both facilitieswere shut-down for extended periods of time in 2009-2010 which caused aserious on-going world-wide shortage of supply of Mo-99 for medicalfacilities. Although both facilities are now active again, significantconcerns remain regarding reliable long-term supply of Mo-99.

It is known that medical cyclotrons can produce small amounts of Tc-99mfrom Mo-100 for research purposes. It has been recently demonstratedthat Tc-99m produced in a cyclotron is equivalent to nuclear Tc-99m whenused for nuclear medical imaging (Guerin et al., 2010, Cyclotronproduction of ^(99mc) Tc: An approach to the medical isotope crisis. J.Nucl. Med. 51(4):13N-16N). However, analyses of numerous studiesreporting conversion of Mo-100 to Tc-99m show considerable discrepanciesregarding conversion efficiencies, gamma ray production, and purity(Challan et al., 2007, Thin target yields and Empire II predictions inthe accelerator production of technetium-99m. J. Nucl. Rad. Phys. 2:1-;Takacs et al., 2003, Evaluation of proton induced reactions on ¹⁰⁰ Mo:New cross sections for production of ^(99m) Tc and ⁹⁹ Mo. J. Radioanal.Nucl. Chem. 257: 195-201; Lebeda et al., 2012, New measurement ofexcitation functions for (p,x) reactions on ^(nat) Mo with specialregard to the formation of ^(95m) Tc, ^(96m+g) Tc, ^(99m) Tc and ⁹⁹ Mo.Appl. Radiat. Isot. 68(12): 2355-2365; Scholten et al., 1999, Excitationfunctions for the cyclotron production of ^(99m) Tc and ⁹⁹ Mo. Appl.Radiat. Isot. 51:69-80).

SUMMARY OF THE DISCLOSURE

The exemplary embodiments of the present disclosure pertain to processesfor the production of technetium-99m (Tc-99m) from molybdenum-100(Mo-100) by proton irradiation with accelerators such as cyclotrons.Some exemplary embodiments relate to systems for working the processesof present disclosure. Some exemplary embodiments relate to apparatuscomprising the systems of the present disclosure.

DESCRIPTION OF THE DRAWINGS

The present disclosure will be described in conjunction with referenceto the following drawings in which:

FIG. 1 is a schematic flowchart outlining an exemplary process of thepresent disclosure;

FIG. 2 is plan view of an exemplary elongate target plate according toone embodiment of the present disclosure;

FIG. 3A is a cross-sectional side view and FIG. 3B is a cross-sectionalend view of the exemplary target plate from FIG. 2;

FIG. 4 is a perspective view of an exemplary target capsule apparatusfor mounting therein the exemplary target plate shown in FIGS. 2, 3A,3B;

FIG. 5 is a partial view into the top of the target capsule apparatusfrom FIG. 4;

FIG. 6 is a cross-sectional side view of the target capsule apparatusfrom FIG. 5;

FIG. 7 is a perspective view of an exemplary target pickup apparatuswith a pusher component for engaging the target capsule assemblyapparatus in FIGS. 4-6;

FIG. 8 is a cross-sectional side view of the target pickup apparatusfrom FIG. 7 engaged with the pusher component;

FIG. 9 is a perspective view of an exemplary receiving cell apparatusfor engaging and cooperating with the target station apparatus shown inFIGS. 12-14;

FIG. 10 is a side view of the receiving cell apparatus shown in FIG. 9;

FIG. 11 is a top of the receiving cell apparatus shown in FIG. 9;

FIG. 12 is a perspective view of an exemplary target station apparatusfor receiving the target pickup apparatus shown in FIGS. 7-8 engagedwith the target capsule apparatus shown in FIGS. 4-6;

FIG. 13 is a side view of the target station apparatus shown in FIG. 12;

FIG. 14 is a top view of the target station apparatus shown in FIG. 12;

FIG. 15A is a plan view of an exemplary circular target plate accordingto one embodiment of the present disclosure, FIG. 15B is a top view, andFIG. 15C is a cross-sectional side view of the exemplary circular targetplate from FIG. 15A;

FIG. 16 is a perspective view of an exemplary target capsule apparatusfor mounting therein a circular target disc;

FIG. 17 is an end view of the target capsule apparatus shown in FIG. 16;

FIG. 18 is a cross-sectional side view of the target capsule apparatusshown in FIG. 16;

FIG. 19 is a perspective view of an exemplary target pickup apparatusengaged with a pusher component;

FIG. 20 is a cross-sectional side view of the target pickup apparatusfrom FIG. 19;

FIG. 21 is a perspective view of an exemplary receiving cell apparatusfor engaging and cooperating with the target station apparatus shown inFIGS. 24-27;

FIG. 22 is a side view of the receiving cell apparatus shown in FIG. 21;

FIG. 23 is a top view of the receiving cell apparatus shown in FIG. 21;

FIG. 24 is a perspective view of an exemplary target station apparatusfor receiving the target pickup apparatus shown in FIG. 19 engaged withthe target capsule apparatus shown in FIGS. 16-18;

FIG. 25 is a top view of the target station apparatus shown in FIG. 24;

FIG. 26 is a cross-sectional top view of the target station apparatusshown in FIG. 24 with an exemplary target cell apparatus delivered tothe target housing in an unloaded position;

FIG. 27 is across-sectional top view of the target station apparatusshown in FIG. 24 with the exemplary target cell apparatus moved to aloaded position;

FIG. 28 is a perspective view of an exemplary booster station; and

FIG. 29A is a perspective view of the exemplary booster station fromFIG. 28 with the cover removed and in a disengaged view, while FIG. 29Bshows the booster station in an engaged mode.

DETAILED DESCRIPTION

An exemplary embodiment of the present disclosure pertains to processesfor producing Tc-99m by low-energy proton radiation of Mo-100 usingproton beams produced by accelerators such as cyclotrons. Suitableproton energy for the processes of the present disclosure is from arange of about 10 MeV to about 30 MeV incident on the target. Aflowchart outlining an exemplary process is shown in FIG. 1. The processgenerally follows the steps of:

1) Processing a supply of enriched Mo-100 metal powder to produce aMo-100 powder with a consistent grain size of less than about 10microns.

2) Depositing a coating of the processed Mo-100 powder onto a targetplate comprising a transition metal, by electrochemical and/orelectrophoretic deposition.

3) Sintering the coated target plate in an inert atmosphere for about 2hours to about 10 hours at a temperature of about 1200° C. to about2000° C.

4) Securely engaging the sintered target plate into a target holder. Atarget holder engaged with a sintered target plate is referred to hereinas a target capsule assembly.

5) Installing the target capsule assembly into a receiving cellapparatus wherein the target capsule assembly is engaged by a targetpickup apparatus. The target pickup cooperates with a target transferdrive apparatus for delivery of the target capsule assembly into atarget station apparatus engaged with a cyclotron.

6) In an atmosphere that is substantially oxygen-free, irradiating thesintered target plate with a supply of protons generated by anaccelerator.

7) With a transfer drive apparatus, disengaging the target capsuleassembly from the target station and transferring the target capsuleassembly into receiving cell apparatus for separating and recoveringmolybdate ions and pertechnetate ions from the proton-irradiated targetplate.

8) Separating the pertechnetate ions from the molybdate ions, purifying,and further processing the pertechnetate ions. These steps are doneunder precisely controlled environmental conditions to minimize lossesof the pertechnetate ions.

9) Recovering and purifying the molybdate ions to make them suitable forre-use in coating target plates.

Previous uses of accelerators for producing Tc-99m from Mo-100 werefocused on producing small quantities of product sufficient for researchuse and for comparison of thus-produced Tc-99m functionality in medicaldiagnostic imaging with the standard Tc-99m produced from Mo-99 usingnuclear reactors. Commercially available enriched Mo-100 metal powderstypically comprise mixtures of particle sizes ranging from less than amicron to more than a millimeter. Consequently, using such powders forcoating target backing discs or backing plates results in unevendistribution of Mo-100 across the plate surfaces and varying thicknessesof Mo-100 deposition. Such variabilities result in target plate failuresduring irradiation with proton beams, in lowered conversion efficienciesof molybdenum atoms into technetium atoms, and in unpredictable yieldsof pertechnetate ions. Accordingly, it has become common practice topress commercial-grade Mo-100 powders at pressures of about 25,000 N toabout 100,000 N into pellets having diameters in the range of 6.0 to 9.5mm. The Mo-100 pellets are then reduced in a hydrogen atmosphere attemperatures in the range of 800° C. to 900° C. Mo-100 is typicallymounted onto a target backing disc either as commercial-grade Mo-100powders or alternatively as sintered Mo-100 pellets by pressing, or byarc melting, or electron beam melting. The melting methods generally usecurrents from a range of 40 mA to 70 mA which are applied in a varietyof sweeping patterns and focusing patterns. Consequently, using suchpowders and/or pellets for coating target plates results in unevendistribution of Mo-100 across the plate surfaces and in varyingthicknesses of Mo-100 deposition. Such variabilities result in: (i)target plate failures during irradiation with proton beams, (ii) inlowered conversion efficiencies of molybdenum atoms into technetiumatoms, and (iii) in unpredictable yields of pertechnetate ions. Otherproblems commonly encountered are associated with the target discsthemselves. The targets typically used in the research-scale Tc-99mproduction in cyclotrons comprise small thin discs of copper or tantalumhaving diameters generally in the range of about 5-6 mm. Such discs cannot be loaded with sufficient Mo-100 to enable large-scale production ofTc-99m, because they are mechanically fragile and may fail, i.e.,fragment, under proton irradiation due to the very high levels of heatconcomitantly generated. There are numerous challenges and issues thatmust be addressed in order to successfully scale Tc-99m production fromMo-100 using cyclotron-based systems. Issues related to the molybdenumthat need to be addressed include overcoming the problems of: (i)inability to deposit thick layers of Mo-100 onto target plates bygalvanic plating from aqueous solutions, (ii) isotopically enrichingmolybdenum to facilitate production of specific technetium isotopes, and(iii) requirements for concentrated acid solutions and for extendedperiods of time for dissolving irradiated plates of molybdenum.Challenges that need to be solved to facilitate commercial-scaleproduction of Tc-99m production from Mo-100 using cyclotron-basedsystems, include selection of and configuring of suitable target backingplate materials: (i) to which Mo-100 will strongly adhere to before andduring proton irradiation, (ii) that are impervious to penetration byprotons, (iii) that are sufficiently mechanically robust to withstandheating during proton irradiation, (iv) that are thin enough to enableheat dissipation and/or cooling of the Mo-100 during irradiation, and(iv) are chemically inert, i.e., will not chemically contaminate orotherwise interfere with dissolution of the irradiated Mo-100.

Accordingly, some exemplary embodiments of the present disclosure relateto a process for refining commercial Mo-100 powders into uniformparticles of less than 10 microns, to mechanically robust target platesfor mounting thereon of the refined Mo-100 particles, and toelectrophoretic methods for mounting the refined Mo-100 particles ontothe targets plates.

According to one aspect, commercial-grade Mo-100 metal powder is firstoxidized in a solution comprising about 3% to about 40% hydrogenperoxide (H₂O₂). A particularly suitable concentration of H₂O₂ is about30%. The mixture of Mo-100 and H₂O₂ is then heated to a range of about40° C. to about 50° C. to denature residual H₂O₂, then dried to recoversolid molybdenum oxide. The solid molybdenum oxide is converted back toMo-100 metal using a three-stage heating process. In the first stage,the dried molybdenum oxide is heated for about 30 min at about 400° C.in an environment comprising about 2% hydrogen in an argon gas mixtureto allow for the formation of MoO₃. After 30 min at 400° C., thetemperature is then raised for the second stage of the process, to about700° C. for about 30 min to facilitate the reduction of MoO₃ to MoO₂.The temperature is then further raised for the third stage of theprocess, to about 1100° C. for about 30 min to reduce the MoO₂ to Mo-100metal. Because MoO₂ sublimes at 1500° C., it is important to keep thetemperature during the third stage within the range of about 1100° C.and about 1455° C., of about 1100° C. and about 1400° C., of about 1100°C. and about 1350° C., of about 1100° C. and about 1300° C., of about1100° C. and about 1250° C., of about 1100° C. and about 1200° C. It isimportant to limit the atmospheric hydrogen content during the firststage of the process less than about 5%, about 4%, about 3%, andpreferably at about 2% or less to control the rate of reduction of MoO₃to MoO₂. Because the reduction of MoO₂ to Mo-100 is an endothermicreaction, it is suitable to use a high hydrogen atmosphere, oralternatively, a pure hydrogen atmosphere for the third stage of thisprocess. The processed Mo-100 powder produced by this three-stageprocess is characterized by a consistent grain size of less than 10microns.

Another aspect of this embodiment of the present disclosure relates toelectrophoretic processes for coating target backing plates with therefined Mo-100 powders having uniform particle sizes of less than 10microns. A refined Mo-100 powder is suspended in a suitable polarorganic solvent exemplified by anhydrous nitromethane, nitroalkanes,isopropanol, and the like, and a suitable binder exemplified by zein,and then stirred vigorously at an ambient temperature selected from arange of about 15° C. to about 30° C. A cathode comprising a transitionmetal and an anode comprising a conductive metal exemplified by copper,are then submerged into the suspension. A potential of about 150 V toabout 5000 V, about 200 V to about 4000 V, about 250 V to about 3000 V,about 300 V to about 2500 V, about 400 V to about 2000 V, about 500 V toabout 1500 V is applied across the anode and cathode for a duration oftime from about 2 min to about 30 min to cause deposition of the Mo-100and the binder onto the cathode. A particularly suitable potential toapply across the anode and cathode is about 1200 V. The coated cathodesare then removed from the mixture and sintered by heating at atemperature from the range of about 1500° C. to about 2000° C., about1300° C. to about 1900° C., about 1400° C. to about 1800° C., about1400° C. to about 1700° C., for a period of time from the range of 2-7h, 2-6 h, 4-5 h in an oxygen-free atmosphere provided by an inert gasexemplified by argon. We have discovered that this process enablesdeposition of a molybdenum metal layer onto target backing plates (alsoreferred to herein as “target plates”) with a density that is about 85%of the possible theoretical density.

Another aspect of this embodiment pertains to target plates onto whichis mountable Mo-100. The target plate configuration is suitable forirradiation by protons delivered: (i) with or without a beamlineextending from a cyclotron, or alternatively (ii) in a self-shieldedcyclotron chamber wherein beamlines are not used. The width of thetarget plate is sufficient to receive an entire beamspot of protonenergy produced with a cyclotron, even when delivered to the targetplate at a selected angle from about 7° to about 90° relative to theincident beam. Beam spots typically generated in cyclotron beamlines arecollimated at about 15-mm diameter. It is common to place aMo-100-coated target plate at an angle to a protein beamline in whichcase, the irradiated surface area on the target plate will be anelongate spot of about 10 mm to about 15 mm by about 20 mm to about 80mm. In self-shielded cyclotrons that do not use beamlines, the spacesfor installing target plates are typically about 30 cm×30 cm×30 cm to byabout 30 cm×30 cm×80 cm. Accordingly, for large-scale production ofTc-99m, it is desirable to have target plates that can be used in: (i)cyclotrons using beamlines such as those exemplified by TR PETcyclotrons manufactured by Advanced Cyclotron Systems Inc. (ACSI,Richmond, BC, CA), by Best Cyclotron Systems Inc. (Springfield, Va.,USA), by IBA Industrial (Louvain-la-Neuve, Belgium), and (ii) inself-shielded cyclotrons that do not use beamlines as exemplified byGE®'s PETtrace® cyclotron systems (GE and PETtrace are registeredtrademarks of the General Electric Company, Schenectady, N.Y., USA). Theexemplary target plates may be circular discs for irradiation by protonbeams at a 90° to the target discs, or alternatively, elongate platesfor irradiation by proton beams delivered angles of less than 90° to thetarget plates.

However, a significant problem that occurs during proton irradiation ofMo-100 is the generation of excessive heat. Accordingly, it is necessaryto coat Mo-100 onto target backing plates that are good thermalconductors and readily dissipate heat. The problem with most suitablethermo-conductive metals is that they have relatively low meltingpoints. Accordingly, there is a risk that target backing platescomprising a thermo-conductive metal that have been electophoreticallycoated with Mo-100, will melt during the sintering process disclosedherein for increasing the density of, and making adherent the coatedMo-100 powder. It is known that tantalum has a very high melting point,i.e., of about 3000° C. and greater. Therefore, it would appear thattantalum might be a preferred metal substrate for target backing plateconfigurations. However, a problem with tantalum is that this transitionmetal is not very heat conductive. Therefore, the use of tantalum fortarget backing plates requires keeping the target backing plates as thinas possible in order to provide some cooling by a coolant flow direct toand about the back of the target backing plates, while at the same time,providing sufficient thickness to absorb heat without fracturing ordisintegration and to stop residual protons that may have exited theMo-100 layer. Accordingly, we investigated various designs andconfigurations of tantalum target backing plates for coating thereontoof Mo-100. One approach was to machine a series of interconnectedchannels into the back of a tantalum target backing plate as exemplifiedin FIGS. 2 and 3. A flow of coolant is directed through the channelsduring proton irradiation, and thus dissipates some of the heatgenerated. However, we found that providing channels for coolant flowabout the back of the tantalum target backing plate compromised thestructural strength of the backing plates, i.e., they were quiteflexible and would fracture under the stresses of coolant flow andproton irradiation. We have surprisingly discovered that the sinteringprocess to densify an make adherent Mo-100 coated onto such tantalumtarget backing plates, also significantly hardens the tantalum substratethereby making target backing plates mechanically robust and extremelydurable in use during proton irradiation and concurrent pressurizedcirculation of a coolant about the back of the target backing platethrough the channels provided therefore. We have determined thatsintered Mo-100-coated target plates comprising tantalum are robust andare structurally stable when irradiated with over 130 microamps of 16.5MeV protons, and when irradiated with over 300 microamps of 18.5 MeVprotons while temperature is maintained at or below about 500° C. by apressurized flow of a coolant about the back of the target backingplates.

The mass of Mo-100 required to produce a suitable target will depend onthe size of the proton beam spot. The target should at least match orexceed the proton beam spot size. The density of Mo-100 is about 10.2g/cm³. Accordingly, the mass of Mo-100 required to coat a target platewill be about “density of Mo-100×area of the target×thickness required”and is calculated for the type of beam line used i.e., for orthogonalirradiation or alternatively, for irradiation by proton beams deliveredat angles of less than 90° to the target plates. It is to be noted thatthe mass of Mo-100 required will not be affected by delivery of protonsat an angle to the target because the required thickness of the coatingdecreases at the same rate as the surface area increases, since only oneaxis of the beam projection is extended as a consequence of changing theangle of the target to the beam.

Table 1 provides a listing of the target thicknesses of molybdenum fordeposition onto circular target plates for orthogonal irradiation with aproton beam (i.e., at about 90° to the plate) for each of threeirradiation energies commonly used by cyclotrons.

TABLE 1 Entrance energy (MeV) Exit energy (MeV) Range (μm) 16.5 10 31318 10 401 22 10 664

Table 2 provides a listing of the target thicknesses of molybdenum fordeposition onto elongate target plates for proton irradiation atdifferent angles to the target for each of the three irradiationenergies listed in Table 1.

TABLE 2 Required thickness (μm) Angle 22-10 MeV 18-10 MeV 16.5-10 MeV 90664 401 313 85 661 399 312 80 654 395 308 75 641 387 302 70 624 377 29465 602 363 284 60 575 347 271 55 544 328 256 50 509 307 240 45 470 284221 40 427 258 201 35 381 230 180 30 332 201 157 25 281 169 132 20 227137 107 15 172 104 81 10 115 70 54 7 81 49 38

An exemplary target plate 10 is shown in FIGS. 2-3, and has an elongateshape with rounded opposing ends. FIG. 2 is a top view of the exemplarytarget plate 10. FIG. 3A is a cross-sectional side view of the targetplate 10, and FIG. 3B is a cross-sectional end view of the target plate10. The thickness of the target plate 10 is sufficient to stop theentire proton beam at the maximum energy of 19 MeV, when no molybdenumis present. However, because of the high heat generated during protonirradiation, water channels 12 are provided in the underside of thetarget plate 10 to enable the circulation of a coolant underneath thetarget plate 10, to dissipate the excess heat. When coated with Mo-100,the target plate is capable of dissipating 300 μA of 18 MeV protons whendelivered in an elliptical beam spot of about 10 mm by about 20 mm at anangle of 10° to the target plate while maintaining temperatures at aboutor below 500° C.

This exemplary target plate is about 105 mm long by 40 mm wide by 1.02mm thick. The cathode i.e., the target plate can comprise any transitionmetal such as those exemplified by copper, cobalt, iron, nickel,palladium, rhodium, silver, tantalum, tungsten, zinc, and their alloys.Particularly suitable are copper, silver, rhodium, tantalum, and zinc.It is to be noted that if tantalum is used as the target plate material,the sintering process will also significantly harden the tantalum targetplate making it extremely durable and able to withstand fracturingstresses resulting from proton irradiation and/or excessive heatproduced during proton irradiation and the pressurization due to theflow of coolant about the back of the target plate.

Another problem that must be addressed during production of Tc-99m fromMo-100 is preventing Mo-100 coated onto a target plate, from oxidizingduring and after irradiation with proton beams. Molydenum oxide has asignificant vapor pressure at only a few hundred ° C. and consequently,exposure to high heat and oxygen during proton irradiation will resultin the formation of molybdenum oxide resulting in decreases in theconversion efficiency of Mo-100 to Tc-99m.

Accordingly, some exemplary embodiments of the present disclosure relateto a system comprising: (i) components for mounting and housingMo-100-coated target plates, these components referred to hereinafter as“target capsule assemblies” or “target capsule apparatus”, and (ii)components for engaging and disengaging the target capsule assemblieswith sources of proton irradiation generated by cyclotrons whilemaintaining an oxygen-depleted atmosphere about the Mo-100-coated targetplates mounted therein. Accordingly, the system and components disclosedherein are configured to enable isolation of a Mo-100-coated targetplate from exposure to oxygen during irradiation with protons, by theprovision and maintenance of atmospheric environments that aresubstantially oxygen-free. The oxygen-free environments can be providedby application and maintenance of a vacuum during and after irradiation.Alternatively, the environments can be saturated with ultra-high purityinert gases.

The following portion of the disclosure with references to FIGS. 4-14pertains to the use of the exemplary embodiments and aspects of thepresent disclosure for irradiation of Mo-100-coated target plates withprotons delivered in a beamline to the target plates at an angle of lessthan 90°. Such beamlines are available PET cyclotrons exemplified bythose manufactured by ACSI.

One aspect relates to a target capsule apparatus for mounting therein aMo-100-coated target plate. Another aspect relates to a target capsulepickup apparatus for remote engagement of the target capsule and forconveying the capsule assembly to and engaging it with a target stationapparatus. Another aspect relates to a target station apparatuscomprising a vacuum chamber for engaging therein the assembled andengaged target capsule apparatus and target pickup apparatus. The targetstation apparatus is sealingly engagable with a source of protons froman accelerator such as those exemplified by cyclotrons.

An exemplary elongate target capsule apparatus for mounting therein anelongate Mo-100-coated target plate for irradiation with protonsdelivered at an angle of less than 90° by PET cyclotrons exemplified bythose manufactured by ACSI, is shown in FIGS. 4-6. This exemplary targetcapsule apparatus 20 comprises a bottom target plate holder 21 and a topcover plate 22 provided with a plurality of spaced-apart bores 23through which socket-head cap screws 24 are inserted and threadablyengaged with the bottom target plate holder 21. The elongate targetcapsule apparatus 20 has a proximal end 25 for engagement with a targetcapsule pickup apparatus, and a distal end 26 having a bore 26 a forreceiving an emission of protons from a suitable accelerator (notshown). The distal end 26 of the target capsule apparatus 20 also hastwo ports 26 b for sealingly engaging a supply of a chilled coolant flowthat is directed by channel 27 to contact and flow underneath targetplate 10 through channels 12 provided in the undersurface of the targetplate 10 (refer to FIGS. 3(a) and (b)). The upper surface of the bottomtarget plate holder 21 may be inclined at an angle from a range of about5° to about 85° relative to a horizontal plane. The lower surface of thetop cover plate 22 is inclined at a matching angle to the upper surfaceof the bottom target plate holder 21. An elongate target plate 10 isplaced on top of O-rings 28 fitted into channels provided therefore inthe upper surface of the bottom target plate holder 21. O-rings 28 arealso fitted into channels provided therefore in the lower surface of thetop cover plate 22. The O-rings 28 securely and sealingly engage theelongate target plate 10 between the bottom target plate holder 21 andthe top cover plate 22 when the socket-head cap screws 24 are insertedthrough the spaced-apart bores 23 and are threadably engaged with thebottom target plate holder 21. The shape of the outer diameter of theproximal end (25) of the target capsule apparatus 20 is to engage withrollers (not shown) provided therefor in the target station and torotate the target capsule apparatus 20 to align the ports 26 a, 26 bwith the target station to form the vacuum and water seals. Thesymmetrical configuration of the target capsule apparatus 20 makes itpossible to rotate the apparatus 20 in a clockwise direction or in acounter-clockwise direction. The coolant can ingress the target capsuleapparatus 20 through either of ports 26 b and egress through theopposite port 26 b.

An exemplary target pickup apparatus 40 is shown in FIGS. 7-8. Thetarget pickup apparatus 40 comprises a pickup head device 41 configuredfor engaging with and disengaging from chamber 25 a provided therefor inthe proximal end 25 of the target capsule apparatus 20 shown in FIGS.4-6. The pickup head device 41 is provided with structures that radiallyextend and retract from within the pickup head configured to engage anddisengage with the chamber 25 a in the proximal end 25 of the targetplate capsule apparatus 20. Suitable engagement devices are exemplifiedby pins, prongs, struts and the like. FIG. 8. showsextendible/retractable prongs 43. The target pickup apparatus 40 is alsoprovided with a target capsule apparatus pusher 44 that is engagable anddisengagable by the engagement devices exemplified by prongs 43. Theextendible/retractable prongs 43 provided in the pickup head device 41are actuated and manipulated by a remotely controllable pull ring 49mounted onto a coupling shaft 48 extending backward from the pickup headdevice 41. The target pickup apparatus 40 additionally comprises atarget pickup guide 46 provided with forward extending shaft 47 that isslidingly received and engaged with the coupling shaft 48 extendingbackward from the pickup head device 41. The rear of the target pickupguide 46 cooperates with an engagable/disengagable steel tape (shown asa shaft 50 in dashed lines in FIG. 8) that cooperates with the targetpickup apparatus 40 for delivery of a target capsule apparatus 20 from atarget station receiving cell apparatus 80 (See FIG. 9) to a targetstation apparatus (shown as item 58 in FIG. 12), and then forpost-irradiation recovery of the target capsule assembly 20 from thetarget station apparatus 58 and delivery back to the target stationreceiving cell apparatus 80.

FIGS. 9-11 show an exemplary target station receiving cell apparatus 80that is installable in a lead-lined fume hood. Suitable lead-lined fumehoods are exemplified by “hot cells” available from Von GahlenInternational Inc. (Chatsworth, Ga., USA) and from Comecer Inc. (Miami,Fla., USA). The target station receiving cell apparatus 80 comprises aframework 82 onto which are mounted an upper shelf 83 and a lower shelf84. A drive unit assembly 85 is mounted onto the upper shelf 83. Thedrive unit assembly 85 houses a length of steel tape 50 that is rolledup onto a drum (not shown) housed within the drive unit assembly 85. Theproximal end of the steel tape 50 is engaged with a drum (not shown)provided within the drive unit assembly 85, while the distal end of thesteel tape 50 is coupled with the target pickup apparatus 40 as shown inFIG. 8. The drive assembly has: (i) a first one-way clutch and gearassembly 81 that is engaged with the drum, (ii) a second one-way clutchand gear assembly 86 that is controllably engagable with the steel tapeextending therethrough, and (iii) a drive motor 99 that cooperates witha chain (not shown) to provide a driving force to the first one-wayclutch and gear assembly 81 and the second one-way clutch and gearassembly 86. The distal end of the steel tape is coupled to the pickuphead device 41 of the target pickup apparatus 40 and extends downwardwithin the target leading tube 95 when not in use. The target pickupapparatus 40 is deployed and recovered through a target leading tube 95by the operation of the drive unit assembly 85. A gate valve assembly100 is mounted onto a port in the hot cell (not shown) directlyunderneath the target leading tube 95. The gate valve (not shown) withingate valve assembly 100 is opened and closed by actuator 101. Mountedonto the lower shelf 84 are carriage rails 115 on which is conveyedbackward and forward a docking station carriage table 114. A dockingstation 110 is mounted onto the docking station carriage table 114. Thedocking station 110 is moveable sideways by a pair of linear actuators116. The docking station comprises a housing having three linearlyaligned bores 111, 112, 113. Bore 111 is a through hole for connectingthe lower end of target leading tube 95 with the top of the gate valveassembly 100. Bore 112 is provided to receive and store the targetcapsule apparatus pusher 44 component of the target pickup apparatus 40,when it is not in use. Bore 113 is provided to receive an assembledtarget capsule assembly 20 with its proximal end 25 in an upwardposition.

In use, within a hot cell using remote-controlled devices (not shown), aMo-100-coated target plate 10 is mounted into a target capsule assembly20. The loaded target capsule assembly 20 is placed by theremote-controlled devices into the target capsule assembly receivingbore 113 while the target docking station carriage table 114 ispositioned by remote control forward and clear of upper shelf 83. Targetdocking station carriage table 114 is then driven by remote control to aposition under upper shelf 83 such that the linearly aligned bores 111,112, 113 are centrally aligned with the gate valve assembly 100. Thedocking station 110 is then conveyed sideways to precisely position bore113 underneath the target leading tube 95 thus being simultaneouslydirected above gate valve assembly 100. The transfer drive unit assembly85 is then operated to deploy sufficient steel tape to engage the targetpickup mechanism 41 with the target capsule apparatus 20, and then, thetransfer drive unit assembly 85 is reversed to draw the target capsuleapparatus 20 up into target leading tube 95. Then, the docking station110 is moved to align bore 111 with the target leading tube 95 thusbeing simultaneously positioned directly above gate valve assembly 100,after which, actuator 101 is operated to open the gate valve. Releaseactuator 96 is operated to release the target capsule 20 from the targetpickup mechanism 41 allowing the target capsule 20 to fall through thebore of gate valve assembly 100 and into transfer tube 68. Then, dockingstation 110 is moved so that target capsule pusher receiving bore 112 isdirectly under the target leading tube 95. The transfer drive 85 isoperated to engage the target capsule apparatus pusher 44 by deployingsteel tape from the drum within the transfer drive 85 by the pinchrollers 104 in cooperation with the pinch roller linear actuator 103,the pinch roller cam linkage 105, and the second one-way clutch and gearassembly 86, so that prongs 43 in the pickup head device 41 of thetarget pickup apparatus 40 engage the target capsule apparatus pusher44. The first one-way clutch and gear assembly 81 is disengaged andoperates freely when the second one-way clutch and gear assembly isengaged. The target pickup apparatus 40 engaged with the pusher 44 isthen drawn up into target leading tube 95 by disengaging the pinchrollers 104 by operating the pinch roller linear actuator 103 incooperation with pinch roller cam linkage 15, and then re-winding thesteel tape onto the drum of the transfer drive apparatus 85 with thefirst one-way clutch and gear assembly 81 in cooperation with the drivemotor 99. The second one-way clutch and gear assembly 86 is disengagedand operating freely during this operation. The docking station 110 isthen moved so that bore 111 is directly under the target leading tube95. The transfer drive apparatus 85 is then operated to deploy the steeltape by the pinch rollers 104 in cooperation with the pinch rollerlinear actuator 103 and the second one-way clutch 86 (first one-wayclutch and gear assembly 81 is disengaged and operates freely) so thatthe target pickup apparatus 40 with the pusher 44 pushes the targetcapsule assembly 20 through the transfer tube 68 to deliver the targetcapsule assembly 20 to a target station assembly (shown as 58 in FIGS.12-14) that is operably coupled to a cyclotron.

FIGS. 12-14 show an assembly 58 of an exemplary target station apparatus60 coupled by a spigot flange 66 to a vacuum chamber apparatus 70 thatis engaged with a beam line to an accelerator such as a cyclotron (notshown). The assembly is mounted into the facility by framework 59. Thetarget station apparatus 60 is connected to a transfer tube 68 by atransfer tube mount 69. The other end of the transfer tube 68 is engagedwith the flange 120 of the gate valve assembly 100 mounted into thereceiving cell apparatus 80 shown in FIGS. 9-11. The target stationapparatus 60 comprises a housing wherein is delivered the elongatetarget capsule apparatus 20 (shown in FIGS. 4-6) by the target pickupapparatus 40 shown in FIGS. 7-8. A linear drive unit 65 mounted onto thetarget station apparatus 60 engages two rollers (not shown) that contactthe outer diameter of the proximal end of target capsule assembly 20 andcooperate with the curved surface of the outer diameter to rotate thetarget capsule apparatus 20 so that it is aligned with spigot flange 66.After it is aligned, the target capsule apparatus 20 is then moved bythe linear drive unit 65 to sealably engage spigot flange 66 therebyforming a vacuum-tight connection between target capsule port 26 a withthe vacuum chamber apparatus 70 and two water-tight connections withtarget capsule ports 26 b. Target capsule assembly 20 may engage withspigot flange 66 in either of two positions 180 degrees apart becauseboth positions are operationally identical. The loaded target capsuleassembly 20 is now ready for proton irradiation. The vacuum chamber 70is evacuated by suitable vacuum pumps (not shown) interconnected to avacuum port 73. The proton beam is collimated during the irradiationprocess by four proton beam collimator assemblies 71 mounted about thevacuum chamber 70. The passage of the proton beam is limited in positionby baffle 72 such that the protons are only incident on the collimatorsor target plate 10 of target capsule assembly 20.

After proton irradiation is complete, the beamline is isolated from thevacuum chamber 70 with the aforementioned vacuum valve and the vacuumchamber pressure is raised to atmospheric pressure. The cooling water ispurged out of the target capsule 20. The irradiated target capsuleassembly 20 is disengaged from spigot flange 66 by linear actuator 65and then recovered by engaging the pickup head device 41 of targetpickup apparatus 40 with the chamber 25 a in the proximal end of thetarget capsule assembly 20. The target capsule assembly 20 is thendelivered back to the target station receiving cell apparatus 80 byrecovery of the deployed steel tape 50 by the drive unit assembly 85until the target capsule unit egresses from the transfer tube 68 and outof the gate valve assembly 100. The docking station 110 is then conveyedto position precisely bore 113 underneath the target leading tube 95,after which the irradiated target capsule assembly 20 is deposited intothe target capsule assembly receiving bore 113 and disengaged from thetarget pickup apparatus 40. The target pickup apparatus 40 is thenretracted into the target leading tube 95, and the docking station 110moved back to its resting position. As will be described in more detaillater, the pertechnetate ions and molybdenate ions are dissolved fromthe irradiated target plate in an apparatus provided therefore in thehot cell, recovered and then separately purified.

Another embodiment of the present disclosure pertains to systemscomprising components for mounting and housing circular Mo-100-coatedtarget plates, and components for engaging and disengaging the housedcircular target plates with sources of proton irradiation generated bycyclotrons while maintaining an oxygen-depleted atmosphere about themounted Mo-100-coated target plates.

An exemplary circular target plate 140 is shown in FIGS. 15A-15C. FIG.15A is a perspective view from the top of the circular target plate 140and shows a recessed section 145 about the centre of the circular targetplate 140. FIG. 15B is a top view of the circular target plate 140,while FIG. 15C is a cross-sectional side view of the circular targetplate 140. The circular target plate 140 may comprise any transitionmetal such as those exemplified by copper, cobalt, iron, nickel,palladium, rhodium, silver, tantalum, tungsten, zinc, and their alloys.Particularly suitable are copper, silver, rhodium, tantalum, and zinc.The recessed portion 145 is provided for receiving therein a refinedMo-100 metal powder, which is then sintered as previously described.

FIGS. 16-18 show an exemplary capsule apparatus 200 for positioning andmounting therein a Mo-100-coated circular target plate 199 that does nothave a recess, or alternatively, a circular target plate with a recessas exemplified in FIGS. 15A-15C. FIG. 16 is a perspective view, FIG. 17is an end view with target plate 140 removed, and FIG. 17 is across-sectional side view of the capsule apparatus 200 that generallycomprises an outer housing 205, an inner cooling distributor 215 (alsoreferred to as a cooling sleeve) for receiving and retaining therein theMo-100-coated circular target plate 199, and housing clamping nut 210for securely engaging the cooling sleeve and circular target plate 140.O-rings 219 are inserted interposed the target plate 199, the outerhousing 205, the inner cooling distributor 215, and the housing clampingnut 210 to sealably secure the target plate 199 into the capsuleapparatus 200. The purpose of the cooling sleeve 215 is to controllablydissipate heat that is generated by proton irradiation of theMo-100-coated target plate 140 thereby minimizing the potential forheat-generated oxidation of molybdenum atoms and technetium atoms. Thecapsule housing clamping nut 210 comprises a chamber 212 configured forengaging and releasing a target pickup apparatus (shown as item 220 inFIG. 19).

Another aspect of this embodiment pertains to an exemplary targetcapsule pickup apparatus 220 for engaging and manipulating an assembledcircular target plate capsule apparatus (FIGS. 19-20). FIG. 19 is aperspective view while FIG. 20 is a cross-sectional side view of thetarget capsule pickup apparatus 220 engaged with a pusher 225. Thetarget capsule pickup apparatus 220 generally comprises a radiallyextendable/retractable pickup head device 223 for engaging an assembledtarget plate capsule apparatus 200 or pusher 225, a shaft 226 extendingbackward from the pickup head for engaging a shaft 231 extending forwardfrom a target pickup guide 230. Shaft 231 extends backward through atarget pickup guide 230 and engages a steel tape 232. The target capsulepickup apparatus 220 additionally comprises a target housing pusher 225for delivering the target capsule apparatus 200 into a target stationapparatus (shown in FIGS. 24-27). The shaft 226 extending backward fromthe pickup head device 223 is provided with an actuating device 227 toradially extend and retract engagement devices 224 within the pickuphead device 223 that are configured to engage and disengage with theassembled target plate housing apparatus. Suitable engagement devicesare exemplified by pins, prongs, struts and remotely actuated andmanipulated by remote control of actuating device 227.

Another aspect of this embodiment pertains to an exemplary targetstation apparatus for receiving and mounting therein an assembledcircular target plate capsule apparatus, and then engaging the circulartarget plate capsule apparatus with a proton beam port on a cyclotronexemplified by GE®'s PETtrace® cyclotron systems. The target stationassembly has multiple purposes, i.e., (i) receiving and mounting theassembled target plate capsule apparatus into a vacuum chamber, (ii)establishing a stable oxygen-free environment within vacuum chamber byapplication of a vacuum and/or replacement of the atmospheric air withan ultra-high purity inert gas exemplified by helium, (iii) deliveringthe assembled target plate capsule apparatus to a source of cyclotrongenerated proton energy and engaging the target plate capsule apparatuswith the source of proton emission, (iv) establishing and maintaining avacuum seal between the target plate capsule apparatus and the source ofproton emission, (v) precisely manipulating the temperature of thecooling distributor in the housing apparatus during the irradiationoperation, (vi) disengaging and removing the irradiated target platecapsule apparatus from the source of proton emission.

FIGS. 21-24 show another exemplary target station receiving cellapparatus 300 that is installable in a lead-lined fume hood (alsoreferred to as a hot cell). The receiving cell apparatus 300 comprises aframework 305 onto which are mounted an upper shelf 306 and a lowershelf 307. A drive unit assembly 310 is mounted onto the upper shelf306. The drive unit assembly 310 houses a length of steel tape 232rolled up onto a drum (not shown) that is housed within the drive unitassembly 310. The steel tape 232 is deployed and recovered through atarget leading tube 315 that is interconnected to the drive unitassembly 310 and extends downward through the upper shelf 306. Theproximal end of the steel tape (232 shown in FIGS. 19-20) is engagedwith the drum housed within the drive unit assembly 310, while thedistal end of the steel tape 232 is coupled with the target pickupapparatus 220 as shown in FIGS. 19-20. The drive assembly 310 has: (i) afirst one-way clutch and gear assembly 311 that is engaged with thedrum, (ii) a second one-way clutch and gear assembly 312 that iscontrollably engagable with the steel tape extending therethrough, and(iii) a drive motor 313 that cooperates with a chain (not shown) toprovide a driving force to the first one-way clutch and gear assembly311 and the second one-way clutch and gear assembly 312.

Accordingly, the pickup head device 223 of the target pickup apparatus220 extends downward with the target leading tube 315 when not in use. Agate valve assembly 325 is mounted onto a port in the hot cell directlyunderneath the target leading tube 315. The gate valve assembly 325 hasa flange 327 for engaging a transfer tube (shown as item 267 in FIG. 24)that is operably interconnected with a target station 250 (FIG. 24). Thegate valve (not shown) within gate valve assembly 325 is opened andclosed by an actuator 326. Mounted onto the lower shelf 307 are carriagerails 340 on which is conveyed backward and forward a docking stationcarriage table 328. A docking station 330 is mounted onto the dockingstation carriage table 328. The docking stations is also preciselypositionable sideways by a pair of linear translators 341. The dockingstation 330 comprises a housing having four linearly aligned bores 332,334, 336, 338. Bore 332 is a through hole connecting target leading tube315 and the top of the gate valve assembly 325. Bore 334 is provided toreceive and store the target capsule apparatus pusher 225 component ofthe target pickup apparatus 220, when it is not in use. Bore 336 isprovided to receive an assembled target capsule assembly 200 with itsproximal end 212 in an upward position. Bore 338 is provided to receivean irradiated target capsule assembly 200 for dissolution therein of themolybdate ions and pertechnetate ions from the irradiated circulartarget plate 140.

In use, within a hot cell using remote-controlled devices (not shown), aMo-100-coated target plate 140 is mounted into a target capsule assembly200. The loaded target capsule assembly 200 is placed by theremote-controlled devices into target capsule assembly receiving bore336 while docking station carriage table 328 is positioned by remotecontrol forward and clear of upper shelf 306. Docking station carriagetable 328 is then driven by remote control to a position under uppershelf 306 such that linearly aligned bores 332, 334, 336, 338 arecentrally aligned with the gate valve assembly 325. The docking station330 is then conveyed sideways to precisely position bore 336 underneaththe target leading tube 315 thus being simultaneously positioned abovegate valve assembly 325. The transfer drive unit assembly 310 is thenoperated to deploy sufficient steel tape to engage the target pickupapparatus 220 with the target capsule apparatus 200, and then, thetransfer drive unit assembly 310 is reversed to draw the target capsuleapparatus 200 up into target leading tube 315. The docking station 330is moved to align bore 332 with the target leading tube 315 thus beingsimultaneously directly above gate valve assembly 325, after whichactuator 326 is operated to open the gate valve. Release actuator 319 isoperated to release the target capsule apparatus 200 from the targetpickup apparatus 220 thereby allowing the target capsule apparatus 200to fall through the bore of gate valve assembly 325 and into transfertube 267. Then, docking station 330 is moved so that target capsulepusher receiving bore 334 is directly under the target leading tube 315.The transfer drive 310 is operated to engage the target pickup mechanism220 with the target capsule apparatus pusher 225 by deploying steel tapefrom the drum within the transfer drive unit 310 by the pinch rollers318 in cooperation with the pinch roller linear actuator 316, the pinchroller cam linkage 317 and the second one-way clutch and gear assembly312 (first one-way clutch and gear assembly 311 operating freely (i.e.not transferring force), so that prongs 224 in the pickup head device223 of the target pickup apparatus 220 engage the target capsuleapparatus pusher 225. The target pickup apparatus 220 engaged with thepusher 225 is then drawn up into target leading tube 315 by firstdisengaging pinch rollers 318 by operating the pinch roller linearactuator 316 in cooperation with the pinch roller cam linkage 317, andthen re-winding the steel tape onto the drum of transfer drive apparatus310 with the first one-way clutch and gear assembly 311 in cooperationwith the drive motor 313 (the second one-way clutch and gear assembly312 operating freely (i.e. not transferring force). The docking station330 is then moved so that bore 332 is directly under the target leadingtube 95. The transfer drive apparatus 315 is then operated to deploy thesteel tape by the pinch rollers 318 in cooperation with the pinch rollerlinear actuator 316, the cam linkage 317, and the second one-way clutch312 (first one-way clutch and gear assembly 311 operating freely (i.e.not transferring force) so that the target pickup apparatus 220 with thepusher 225 pushes the target capsule assembly 200 through the transfertube 267 to deliver the target capsule assembly 200 to a target stationassembly (shown as 270 in FIGS. 24-27) that is operably coupled to acyclotron.

FIGS. 24-27 show a target station assembly 250 comprising an exemplarytarget station housing 252 for receiving a target capsule apparatus 200delivered by a target pickup apparatus 220, wherein the target capsuleapparatus 200 will then be mounted into a loaded position in the targetstation housing 252 (FIG. 27). The target station assembly 250 ismounted onto a PETtrace® cyclotron (not shown) by framework 251. Thetarget station housing 252 is engaged to a cylindrical support element256 to which is interconnected a first pneumatic drive cylinder 270. Thetarget station housing 252 comprises a receiving chamber 253 (best seenin FIG. 27) and an irradiation chamber 254 (best seen in FIG. 26)provided with a port 259 for engaging a cyclotron proton emission port(not shown). The receiving chamber 253 is connected to a transfer tube267 through which a target capsule apparatus 200 is delivered by atarget pickup apparatus 220. The target capsule apparatus 200 is movedwithin target station housing 252 from the receiving chamber 253 to theirradiation chamber 254 by a target holder device 255 interconnectedwith a second pneumatic drive cylinder 272. Target holder device 255 isoperably connected with limit switches 262 (FIG. 25) for remote sensingof the target capsule apparatus 200. Once the target capsule apparatus200 is in the irradiation chamber 254, it is sealingly engaged with thetarget housing front flange 261 by the first pneumatic drive cylinder270. The cylindrical support element target 256 comprises a cooling tubeassembly 257 that is moved by the first pneumatic drive cylinder intothe target capsule apparatus 220 once it has been installed in theirradiation chamber 254 and simultaneously pushes the target capsuleapparatus against the target housing front flange 261 forming a vacuumtight seal. Accordingly port 259 is sealingly engaged with the cyclotronthus forming a contiguous vacuum chamber with the cyclotron and allowingthe free passage of energetic protons to the target plate 140/199. Thecooling tube assembly 257 engages with the cooling distribution sleeve215 of the target capsule assembly to deliver cooling fluid throughpassages 218. After its installation into the target station irradiationchamber 254, the loaded target capsule assembly 200 is now ready forproton irradiation. After proton irradiation is complete, the coolingfluid is purged from the cooling tube assembly 257 and the cooling tubeassembly withdrawn from the cooling distribution sleeve 215 by the firstpneumatic drive cylinder 270. The irradiated target capsule assembly 200is removed from the irradiation chamber 254 to the receiving chamber 253of the target station housing 252 by operation of the second pneumaticdrive cylinder 272. The irradiated target capsule assembly 200 is thenrecovered from the target station assembly 250 by engaging the pickuphead device 223 of target pickup apparatus 220 with the chamber 212 inthe proximal end of the target capsule assembly 200 in cooperation withthe landing pad apparatus 258 and limit switches 262. The target capsuleassembly 200 is then delivered back to the receiving cell apparatus 300by recovery of the deployed steel tape 232 onto the drum provided in thedrive unit assembly 310 by engagement of the first one-way clutch andgear assembly 311, until the target capsule unit 200 egresses from thetransfer tube 267 and out of the gate valve assembly 325. The dockingstation 330 is then conveyed to position target plate dissolution module338 precisely underneath the target leading tube 315. The drive unitassembly 310 is then operated to press target capsule assembly 200 intothe dissolution module 338 thereby forming a liquid tight seal betweenthe target plate 140/199 and the dissolution module 338. As will bedescribed in more detail later, the pertechnetate ions and molybdenateions are then dissolved from the irradiated target plate, recovered andthen separately purified.

Due to facility design and space organization limitations, somecyclotron facilities may require locating a hot cell wherein isinstalled an exemplary receiving cell apparatus according to the presentdisclosure, at some distance from the target station assembly mountedonto a cyclotron to which the receiving cell apparatus is connected by atransfer tube. As the length of the transfer tube and the number ofbends that are required to navigate the distance between a receivingcell apparatus and a target station assembly, increase, so increases thestress and strain on the drive unit assembly and steel tape componentsof the receiving cell apparatus used to deliver and recover targetcapsule assemblies to and from the target station assembly. Accordingly,another embodiment of the present disclosure pertains to booster stationapparatus that can be installed into a transfer tube interposed thereceiving cell apparatus and the target station assembly. An exemplarybooster station apparatus 400 is shown in FIGS. 28, 29A, 29B, andgenerally comprises a booster station framework 415 and a boosterstation housing 410. The booster station framework 415 comprises atransfer tube support plate 425 having an orifice through which a firsttransfer tube (not shown) is inserted, a booster housing back plate 420and a framework stabilizing plate 427 having one end engaged with thetransfer tube support plate 425 and the other end engaged with thebooster housing back plate 420. The booster station apparatus isprovided with a flange 422 (best seen in FIG. 29B) provided with anorifice for engaging the end of the first transfer tube. The housing 410is provided with an orifice 412 aligned with the orifice of the flange430 and flange 422. The orifice 412 in housing 410 allows insertion of asecond transfer tube (not shown). The second transfer tube is engaged inthe orifice of flange 430. A pinch roller assembly comprising anextendible/retractable framework comprising a pair of upper pivotablemount assemblies 445 unto which is mounted an upper roller 440, a pairof lower pivotable mount assemblies 455 unto which is mounted a lowerroller 450, and flange 430 connecting a left-hand pair of an upperpivotable mount assembly and a lower pivotable mount assembly (bothshown as 445, 455) with the corresponding right-hand pair (not shown) ofan upper pivotable mount assembly and a lower pivotable mount assembly.A pair of actuators 460 for extending and retracting the pinch rollerassembly 445,455, 430 is mounted onto the booster station framework 415.A drive unit 465 is mounted onto the pinch roller assembly 445,455, 430for rotating the upper roller 440 when the pinch roller assembly445,455, 430 is extended. When the pinch roller assembly 445,455, 430 isin a retracted position as shown in FIG. 29A, the upper roller 440 andthe lower roller 450 are positioned further apart than the diameter ofthe target tube to allow a target capsule apparatus and target pickupapparatus to pass through the booster station. When the pinch rollerassembly 445,455, 430 is fully extended as shown in FIG. 29B, the upperroller 440 and lower roller 450 frictionally engage the upper and lowersurfaces of the steel tape to deliver a motive force provided by thedrive unit 465 to assist delivery of the target capsule apparatus to thetarget station assembly engaged with the cyclotron or to assist deliveryof the target capsule apparatus to the receive cell depending on thedirection of rotation of drive unit 465. The degree of friction providedis regulated by the pneumatic pressure delivered to linear actuators460.

Another exemplary aspect of this embodiment of the present disclosurerelates to a process for the dissolution of and recovery of molybdateions and pertechnetate ions from proton-irradiated target plates,followed by separation of and separate purification of the molybdateions and pertechnetate ions. The exposed surfaces of a proton-irradiatedtarget plate is contacted with a recirculating solution of about 3% toabout 30% H₂O₂ for about 2 min to about 30 min to dissolve the molybdateions and pertechnetate ions from the surface of the target plate therebyforming an oxide solution. The peroxide solution may be recirculated.The peroxide solution may be heated, for example, by heating thedissolution chamber 338 with heater cartridges placed in the body of thechamber. The oxide solution is recovered after which, the dissolutionsystem and the target plate are rinsed and flushed with distilleddeionized water. The rinsing/flushing water is added to and intermixedwith the oxide solution. The pH of the recovered oxide/rinsing solutionis then adjusted to about 14 by the mixing in of about 1N to about 10Nof KOH or alternatively, about 1N to about 10N NaOH, after which, thepH-adjusted oxide/rinsing solution may be heated to about 80° C. forabout 2 min to about 30 min to degrade any residual H₂O₂ in thepH-adjusted oxide/rinsing solution. The strongly basic pH of theoxide/rinsing solution maintains the molybdenum and technetium speciesas K₂[MoO₄] or Na₂[MoO₄] and K[TcO₄] or Na[TcO₄] ions respectively, orforms exemplified by Mo₂(OH)(OOH), H₂MO₂O₃(O₂)₄, H₂MoO₂(O₂), and thelike.

The pH-adjusted (and optionally heated) oxide/rinsing solution is thenpushed through a solid-phase extraction (SPE) column loaded with acommercial resin exemplified by DOWEX® 1×8, ABEC-2000, Anilig Tc-02, andthe like (DOWEX is a registered trademark of the Dow Chemical Co.,Midland, Mich., USA). The pertechnetate ions are immobilized onto theresin beads while molybdate ions in solution pass through and egress theSPE column. The molybdate ion solution is collected in a reservoir. TheSPE column is then rinsed with a suitable solution so as to maintainpertechnetate affinity for the SPE column, but to ensure molybdate andother impurities have been removed. The rinse solution is added tocollected molybdate ion solution. The pertechnetate ions are then elutedfrom the SPE column with tetrabutylammonium bromide (5-10 mL) in CHCl₃(0.1-1.0 mg/mL). Alternatively, the pertechnetate ions can be elutedfrom the SPE column with NaI (0.1-1.0 mg/mL).

The pertechnetate ion solution eluted from the SPE column is pushedthrough an alumina column preceded by an appropriate column to removeelution components. For Dowex®/ABEC, the alumina column is preceded by acation exchange SPE cartridge to remove residual base from the eluent.The alumina column can also be preceded by an SPE cartridge to removeiodide from the eluent, wherein the pertechnetate is immobilized on thealumina. It is optional to use NaI to remove TcO₄, in which case, asnAg/AgCl SPE cartridge is required in from of the alumina column. Theadsorbed pertechnetate ions are washed with water, and then eluted witha saline solution comprising 0.9% NaCl (w/v) through a 0.2 micron filterand collected into vials in lead-shielded containers. The eluant fromthe alumina column comprises pure and sterile Na[TcO₄].

The molybdate ion/rinse water solution collected from the SPE column isdried. Suitable drying methods are exemplified by lyophilization. Theresulting powder is suspended in a NaOH solution of about 3% to about35% or alternatively, a KOH solution of about 3% to about 35%, afterwhich the solution may be filtered and dried. The resulting powder issolubilized in distilled water and dried again to provide a cleanNa₂MoO₄ product or alternatively, a K₂MoO₄ product. The Na₂MoO₄ orK₂MoO₄ is then pushed through a strongly acidic cation exchange columnto enable recovery and elution of H₂[MoO₄] and other polymeric oxidespecies of molybdenum exemplified by heptamolybdate, octamolybdate. Theeluted molybdate oxides are then frozen, dried and stored. The driedmolybdate oxide powders thus recovered and stored can be reduced asdescribed above for coating onto fresh target plates.

Accordingly, another exemplary embodiment of the present disclosurepertains to systems and apparatus, also collectively referred to asdissolution/purification modules, that are engagable and cooperable withthe exemplary receiving cell apparatus disclosed herein, for receivingand mounting therein irradiated Mo-100-coated target plates fordissolution, recovery and purification of molybdate ions andpertehnetate ions. The exemplary dissolution/purification modules ofthis embodiment of the disclosure generally comprise:

(i) a sealable container for remotely mounting therein an irradiatedMo-100-coated target plate (referred to as the “dissolution chamber”);

(ii) a recirculating supply of an H₂O₂ solution comprising a reservoir,a conduit infrastructure interconnecting the reservoir and thedissolution container, pumps for recirculating the H₂O₂ solution,ingress ports for providing inputs of fresh H₂O₂ solution, egress portsfor controllably removing portions of the recirculating H₂O₂ solution,and instrumentation for monitoring radioactivity, temperature, flowrates and the like in the recirculating H₂O₂ solution;

(iii) a supply of distilled water interconnected with the dissolutioncontainer for post-dissolution washing of the dissolution container andthe recirculating supply of the H₂O₂ solution;

(iv) a chemical processing station comprising a plurality of ports forindividually engaging therewith disposable resin cartridges forimmobilizing thereon and mobilizing therefrom pertechnetate ions andmolybdate ions, a conduit infrastructure for separately recoveringpertechnetate ions, molybdate ions, and waste washings from the resincartridges, and a filling/capping station for capturing and storing therecovered pertechnetate ions, molybdate ions, and waste washings.

What is claimed is:
 1. A system for producing technetium-99m frommolybdate-100, comprising: a target capsule apparatus for housingtherein a Mo-100-coated target plate; a target capsule pickup apparatusfor engaging the target capsule apparatus and delivering the target cellapparatus into a target station apparatus; a target station apparatusfor receiving and mounting therein the target capsule apparatus, saidtarget station apparatus engaged with a cyclotron and communicable withsaid cyclotron for irradiating the Mo-100-coated target plate withprotons; a receiving cell apparatus for receiving and mounting thereinthe irradiated target capsule apparatus; a transfer tube interconnectingthe receiving cell apparatus and the target station apparatus; adissolution/purification module for receiving therein aproton-irradiated Mo-100-coated target plate; a conveyance conduitinfrastructure interconnecting: (i) the target capsule pickup apparatuswith the target station apparatus, (ii) the target station apparatus andthe receiving cell apparatus; and (iii) the receiving cell apparatus andthe dissolution/purification module; and a supply of oxygen-freeatmosphere to the target station apparatus.
 2. The system of claim 1,additionally comprising a booster station apparatus engaged with thetransfer tube.
 3. A target capsule apparatus according to claim
 1. 4. Atarget capsule pickup apparatus according to claim
 1. 5. A targetstation apparatus according to claim
 1. 6. A target station receivingcell apparatus according to claim
 1. 7. A dissolution/purificationmodule according to claim
 1. 8. A booster station apparatus according toclaim 2.